title: Phase I trial of metronomic oral vinorelbine in patients with advanced cancer.
abstract: BACKGROUND
  Antitubulin agents exhibit antiangiogenic effects in vitro and in vivo. We evaluated the safety and feasibility of administering a metronomic schedule of oral vinorelbine designed to optimize its antiangiogenic effects.
  
  
  METHODS
  Patient with advanced cancer who had progressive disease after standard therapy received oral vinorelbine 3 times weekly (i.e., Monday, Wednesday, Friday) at the 6 dose levels ranging from 20 mg (1 week on, 1 week off) to 50 mg (3 weeks on, 1 week off) in cohorts of 3-6 patients at each dose level using a standard phase I design. Dose-limiting toxicity (DLT) during cycle 1 included: (1) neutrophil nadir < 500/μL attributed to therapy, (2) platelet nadir < 50,000/μL attributed to therapy, (3) grade 3-4 non-hematologic toxicity attributed to therapy, and (4) neutropenia associated with grade 2 fever (i.e., febrile neutropenia).
  
  
  RESULTS
  Nineteen patients received 50 cycles of therapy (range 1-11 cycles) at 6 dose levels. There were no dose-limiting toxic events. There were no consistent changes in serum TIE-2 or VCAM-1 levels, or urinary VEGF. One patient with renal cell carcinoma had stable disease for 9 months, and another patient with metastatic prostate cancer had a 70% decline in serum prostate-specific antigen, which lasted 4 months.
  
  
  CONCLUSIONS
  Oral vinorelbine may be given using a metronomic schedule, 50 mg thrice weekly for three of 4 weeks, with minimal toxicity in patients with advanced cancer.
authors.affiliation: Department of Oncology, Albert Einstein College of Medicine and Cancer Center, Montefiore Medical Center, 1825 Eastchester Road Rm#: 2S-50, Bronx, NY 10461, USA. lrajdev@montefiore.org
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajdev
authors.forename: Abdissa
authors.initials: A
authors.lastname: Negassa
authors.forename: Qun
authors.initials: Q
authors.lastname: Dai
authors.forename: Gary
authors.initials: G
authors.lastname: Goldberg
authors.forename: Kathy
authors.initials: K
authors.lastname: Miller
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine